5-Aminosalicylic acid (5-ASA) and chronic tubulointerstitial nephritis in patients with chronic inflammatory bowel disease: is there a link?

(serum creatinine 1.1 mg/dl, weight 56 kg) and an oral the development of a particular type of chronic tubulotreatment with 5-ASA (PentasaB) was started at a interstitial nephritis, characterized by an important dose of 3×500 mg/day. Five months later his calcucellular infiltration of the interstitium with macrolated creatinine clearance was still 84 ml/min. He conphages, T-cells, and also B-cells. Furthermore, after tinued to take the same medication during the stopping the drug, there is improvement of the renal subsequent 23 months, and at that time in the context function, but not in all cases [7,8]. Indeed in several of a general malaise he was found to have a severe instances, particularly those in which there is a delayed renal failure, necessitating haemodialysis treatment diagnosis of renal damage, recovery of renal function (Figure 1). The 5-ASA treatment was stopped and does not occur. Instead, several of those patients before starting the haemodialysis treatment, a renal needed some form of renal replacement therapy [8]. biopsy was performed, which showed oedema and An important aspect of this type of toxic nephropathy severe cellular infiltration of the interstitium with is the documented persistence of inflammation of the T-cells, macrophages, and B-cells; the glomeruli were renal interstitium even several months after stopping normal. After 8 months of haemodialysis treatment the drug intake [9]. the renal function improved, allowing cessation of this That 5-ASA seems to be implicated in the generatreatment. However, the serum creatinine remained tion–development–maintenance of this particular reacelevated (between 5.0 and 6.0 mg/dl) and a second tion at the level of the kidney is supported by the renal biopsy was performed, again showing a severe number of case reports in recent literature of patients oedema and cellular infiltration of the interstitium with with inflammatory bowel disease using 5-ASA as the T-cells, macrophages, and B-cells, with signs of fibrosis; only medication, the improvement, at least partial, of the glomeruli were again normal (Figure 2). It was the impaired renal function upon stopping the drug, decided to start a course with methylprednisolone, and a worsening after resuming 5-ASA use [1]. which was tapered o and stopped after 6 weeks, since Furthermore, the molecular structure of 5-ASA is very there was no e ect on the serum creatinine. The close to that of salicylic acid, phenacetin, and aminopatient’s glomerular filtration rate 4 years after the phenol, drugs with a well-documented nephrotoxic start of the colitis ulcerosa was less than 20 ml/min. potential. The clinical importance of this case report consists in However, renal manifestations of chronic inflamthe association of a severe chronic tubulointerstitial matory bowel disease are well recognized. The most nephritis with the start of 5-ASA treatment in a patient frequent renal complications are oxalate stones and with chronic inflammatory bowel disease, the absence their consequences such as pyelonephritis, hydroof substantial recovery of the renal function more than nephrosis, and in the long term amyloidosis. As for 1 year after stopping the treatment, and the developmany drugs, reversible acute interstitial nephritis has ment of severe fibrotic lesions as shown in the second been described [5]. Also glomerulonephritis, showing renal biopsy. a heterogenous expression, has been associated with Over the last decade 5-ASA has replaced sulphasalachronic inflammatory bowel disease [10]. zine as first-line therapy for mild to moderate active Recently we conducted a limited retrospective study inflammatory bowel disease. In the past few years, to obtain further insight into the frequency of this